Angiogenic Cell Therapy by Bone Marrow-Derived Monocyte-lineage Stem Cells
| Project/Area Number |
15390254
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kyoto Prefectural University School of Medicine |
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Principal Investigator |
MATSUBARA Hiroaki Kyoto Prefectural University School of Medicine, Department of Cardiovascular Medicine, Professor of Medicine, 医学研究科, 教授 (10239072)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2004: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2003: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | endothelium / angioplasty / endothelial progenitor cell / bone marrow / reendothelialization / angiogenesis / 血管再生 / 骨髄移植 / 単球 |
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| Research Abstract |
Peripheral blood(PB)-derived CD14^+ monocytes were shown to trans-differentiate into endothelial cell(EC)-lineage cells and contribute to neovascularization. We investigated whether bone marrow(BM)- or PB-derived CD34^-/CD14^+ cells are involved in reendothelialization after carotid balloon injury. Human BM-derived CD34^-/CD14^+ monocyte-lineage cells (BM-MLCs), but not PB-derived CD34^-CD14^+ monocytes, expressed EC-specific markers (Tie2, CD31, VE-cadherin, Endoglin) to an extent identical to mature EC. When BM-MLCs were cultured with VEGF, hematopoietic markers were drastically decreased and new EC-specific markers (Flk and CD34) were induced. BM-MLCs were intra-arterially transplanted into balloon-injured arteries of athymic nude rats. Only when BM-MLCs were activated by MCP-1 in vivo or in vitro, they adhered onto injured endothelium, differentiated into EC-like cells by losing hematopoietic markers and inhibited neointimal hyperplasia. Such MCP-dependent adhesion was not observed in PB-derived CD34^-/CD14^+ monocytes. Regenerated endothelium exhibited cobble-stone appearance, blocked extravasation of dye and induced NO-dependent vasorelaxation. Basal adhesive activities on HUVEC under laminar flow and beta-1-integrin expression (basal and active forms) were significantly increased in BM-MLCs compared with PB-derived monocytes. MCP-1 markedly enhanced adhesive activity of BM-MLCs (2.8 fold) on HUVEC by activating beta-1-integrin conformation. Thus, BM-MLCs can function as EC progenitors and acquire the ability to adhere on injured endothelium in a MCP-1-dependent manner, leading to reendothelialization followed by inhibition of intimal hyperplasia. This will open a novel window to MCP-1-mediated biological actions as well as vascular regeneration strategies using BM cell therapy.
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Report
(3 results)
Research Products
(26 results)
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[Journal Article] Aldosterone directly induces myocyte apoptosis through calcineurin-dependent pathways.2004
Author(s)
Mano A, Tatsumi T, Shiraishi J, Keira N, Nomura T, Takeda M, Nishikawa S, Yamanaka S, Matoba S, Kobara M, Tanaka H, Shirayama T, Takamatsu T, Nozawa Y, Matsubara H.
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Journal Title
Circulation 110(3)
Pages: 317-323
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia.2004
Author(s)
Higashi Y, Kimura M, Hara K, Noma K, Jitsuiki D, Nakagawa K, Oshima T, Chayama K, Sueda T, Goto C, Matsubara H, Murohara T, Yoshizumi M.
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Journal Title
Circulation. 109(10)
Pages: 1215-1218
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Bone Marrow Monocyte-Lineage Cells Adhere on Injured Endothelium by MCP-1-Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells2003
Author(s)
Fujiyama S, Amano K, Uehira K, Yoshida M, Nishiwaki Y, Nozawa Y, Jin D, Takai S, Miyazaki M, Egashira K, Imada T, Iwasaka T, Matsubara H.
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Journal Title
Circ Res 93
Pages: 980-989
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Enhancement of Ischemia-Induced Angiogenesis by eNOS overexpression.2003
Author(s)
Amano K, Matsubara H, Iba O, Okigaki M, Fujiyama S, Imada T, Kojima H, Nozawa Y, Kawashima S, Yokoyama M, Iwasaka T.
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Journal Title
Hypertension 41
Pages: 156-162
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Therapeutic angiogenesis for patients with limb ischemia by autologous transplantation of bone marrow cells : a pilot study and a randomised controlled trial2002
Author(s)
Tateishi-Yuyama E, Matsubara H*, Murohara T, Ikeda U, Shintani S, Masaki H, Kishimoto, Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T.
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Journal Title
Lancet 360
Pages: 427-435
Description
「研究成果報告書概要(欧文)」より
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